Sodium hydride → HCID 86681867, compound

HRID 1749372Notes

Reaction equation

HRID 1749372 reaction equation
[OH:1][C@H:2]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:5]([CH3:15])[CH2:4][CH2:3]1.[H-].[Na+].[C:18]([C:20]1[CH:25]=[CH:24][N:23]=[C:22](F)[CH:21]=1)#[N:19]>CS(C)=O>[C:18]([C:20]1[CH:25]=[CH:24][N:23]=[C:22]([O:1][C@H:2]2[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:5]([CH3:15])[CH2:4][CH2:3]2)[CH:21]=1)#[N:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 120025874-Cyano-2-fluoropyridineHCID 866818662490154-94-2

Product 1

HCID 86681867HCID 86681867, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of tert-butyl (2R,5R)-5-hydroxy-2-methylpiperidine-1-carboxylate (4.50 g, 22.9 mmol) in DMSO (42 mL) was treated with NaH (0.60 g, 25.1 mmol) in portions, then allowed to stir for 15 min. Solid 4-cyano-2-fluoropyridine (3.83 g, 31.4 mmol) was then added and the reaction was stirred at RT overnight. The reaction was quenched by addition of saturated, aqueous NaHCO3, then diluted further with water. The mixture was extracted three times with EtOAc. The organics were washed with brine, dried over MgSO4, filtered, and concentrated. The crude material was purified by silica gel gradient chromatography (0-25% ethyl acetate in hexanes), providing the titled compound as a colorless oil which quickly solidified to give white crystals. 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J=5.2 Hz, 1H), 7.05 (dd, J=5.18, 1.3 Hz, 1H), 6.96 (d, J=1.1 Hz, 1H), 5.16 (s, 1H), 4.51 (s, 1H), 4.34 (d, J=15.0 Hz, 1H), 3.05-3.08 (m, 2H), 2.07-2.20 (m, 1H), 1.89-1.95 (m, 2H), 1.35-1.38 (m, 2H), 1.30 (s, 9H), 1.19 (d, J=7.2 Hz, 3H) ppm. LRMS m/z (M+H) 318.4 found, 318.2 required.

Workup

  1. stirringthe reaction was stirred at RT overnight
  2. customThe reaction was quenched by addition of saturated, aqueous NaHCO3
  3. additiondiluted further with water
  4. extractionThe mixture was extracted three times with EtOAc
  5. washThe organics were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by silica gel gradient chromatography (0-25% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5570b880b39743c18dc43b2b7a8a250f
Source dataset
uspto-grants-2015_10
Patent number
US09156819B2

Reaction notes

Loading…